IBUTILIDE FUMARATE

Details

Stereochemistry	RACEMIC
Molecular Formula	2C20H36N2O3S.C4H4O4
Molecular Weight	885.225
Optical Activity	( + / - )
Defined Stereocenters	0 / 2
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C\C(O)=O.CCCCCCCN(CC)CCCC(O)C1=CC=C(NS(C)(=O)=O)C=C1.CCCCCCCN(CC)CCCC(O)C2=CC=C(NS(C)(=O)=O)C=C2

InChI

InChIKey=PCIOHQNIRPWFMV-WXXKFALUSA-N

InChI=1S/2C20H36N2O3S.C4H4O4/c2*1-4-6-7-8-9-16-22(5-2)17-10-11-20(23)18-12-14-19(15-13-18)21-26(3,24)25;5-3(6)1-2-4(7)8/h2*12-15,20-21,23H,4-11,16-17H2,1-3H3;1-2H,(H,5,6)(H,7,8)/b;;2-1+

HIDE SMILES / InChI

Molecular Formula	C20H36N2O3S
Molecular Weight	384.576
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: http://www.drugbank.ca/drugs/DB00308
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/cdi/ibutilide.html

Ibutilide is a 'pure' class III antiarrhythmic drug, used intravenously against atrial flutter and fibrillation. At a cellular level it exerts two main actions: induction of a persistent Na+ current sensitive to dihydropyridine Ca2+ channel blockers and potent inhibition of the cardiac rapid delayed rectifier K+ current, by binding within potassium channel pores. In other words, Ibutilide binds to and alters the activity of hERG potassium channels, delayed inward rectifier potassium (IKr) channels and L-type (dihydropyridine sensitive) calcium channels. Ibutilide is indicated for the rapid conversion of atrial fibrillation or atrial flutter of recent onset to sinus rhythm. Ibutilide is marketed as Corvert by Pfizer.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Voltage-gated L-type calcium channel alpha-1C subunit 44 Target ID: CHEMBL1940 Sources: http://www.drugbank.ca/drugs/DB00308	Activator 1430
Voltage-dependent L-type calcium channel subunit beta-1 2 Target ID: Q02641 Gene ID: 782.0 Gene Symbol: CACNB1 Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00308	Activator 1430
HERG 92 Target ID: CHEMBL240 Sources: http://www.drugbank.ca/drugs/DB00308	Inhibitor 8297	0.9 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Atrial fibrillation 131 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf	Primary		Approved 8429	CORVERT Approved Use indicated for the rapid conversion of atrial fibrillation or atrial flutter of recent onset to sinus rhythm. Launch Date 8.2002241E11

C_max

Value	Dose	Co-administered	Analyte	Population
5.8 μg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19025427	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:		IBUTILIDE unknown	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
177 μg × min/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18035195	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:		IBUTILIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
13.2 μg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19025427	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:		IBUTILIDE unknown	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
9.1 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18035195	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:		IBUTILIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
12.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19025427	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:		IBUTILIDE unknown	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1 mg single, intravenous Highest studied dose Dose: 1 mg Route: intravenous Route: single Dose: 1 mg Sources: https://pubmed.ncbi.nlm.nih.gov/18035195/	healthy, adult n = 8 Health Status: healthy Age Group: adult Sex: M Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/18035195/	Sources: https://pubmed.ncbi.nlm.nih.gov/18035195/
1 mg 1 times / 10 min multiple, intravenous Recommended Dose: 1 mg, 1 times / 10 min Route: intravenous Route: multiple Dose: 1 mg, 1 times / 10 min Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	unhealthy, adult n = 776 Health Status: unhealthy Condition: atrial flutter or atrial fibrillation Age Group: adult Population Size: 776 Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	Disc. AE: Extrasystoles ventricular, Non-sustained ventricular tachycardia... Other AEs: Chest pain, Bradycardia... AEs leading to discontinuation/dose reduction: Extrasystoles ventricular (3.7%) Non-sustained ventricular tachycardia (3.4%) Non-sustained ventricular tachycardia (3.5%) Polymorphic ventricular tachycardia (1.8%) Other AEs: Chest pain (2.6%) Bradycardia (1.4%) Hypotension (2.6%) Sinus bradycardia (1.2%) Heart arrest (1%) Headache (4.1%) Procedural complication (1.9%) Nausea (4.8%) Dizziness (1.8%) Diarrhea (1.8%) Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf

AEs

AE	Significance	Dose	Population
Heart arrest	1%	1 mg 1 times / 10 min multiple, intravenous Recommended Dose: 1 mg, 1 times / 10 min Route: intravenous Route: multiple Dose: 1 mg, 1 times / 10 min Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	unhealthy, adult n = 776 Health Status: unhealthy Condition: atrial flutter or atrial fibrillation Age Group: adult Population Size: 776 Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf
Sinus bradycardia	1.2%	1 mg 1 times / 10 min multiple, intravenous Recommended Dose: 1 mg, 1 times / 10 min Route: intravenous Route: multiple Dose: 1 mg, 1 times / 10 min Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	unhealthy, adult n = 776 Health Status: unhealthy Condition: atrial flutter or atrial fibrillation Age Group: adult Population Size: 776 Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf
Bradycardia	1.4%	1 mg 1 times / 10 min multiple, intravenous Recommended Dose: 1 mg, 1 times / 10 min Route: intravenous Route: multiple Dose: 1 mg, 1 times / 10 min Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	unhealthy, adult n = 776 Health Status: unhealthy Condition: atrial flutter or atrial fibrillation Age Group: adult Population Size: 776 Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf
Diarrhea	1.8%	1 mg 1 times / 10 min multiple, intravenous Recommended Dose: 1 mg, 1 times / 10 min Route: intravenous Route: multiple Dose: 1 mg, 1 times / 10 min Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	unhealthy, adult n = 776 Health Status: unhealthy Condition: atrial flutter or atrial fibrillation Age Group: adult Population Size: 776 Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf
Dizziness	1.8%	1 mg 1 times / 10 min multiple, intravenous Recommended Dose: 1 mg, 1 times / 10 min Route: intravenous Route: multiple Dose: 1 mg, 1 times / 10 min Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	unhealthy, adult n = 776 Health Status: unhealthy Condition: atrial flutter or atrial fibrillation Age Group: adult Population Size: 776 Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf
Polymorphic ventricular tachycardia	1.8% Disc. AE	1 mg 1 times / 10 min multiple, intravenous Recommended Dose: 1 mg, 1 times / 10 min Route: intravenous Route: multiple Dose: 1 mg, 1 times / 10 min Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	unhealthy, adult n = 776 Health Status: unhealthy Condition: atrial flutter or atrial fibrillation Age Group: adult Population Size: 776 Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf
Procedural complication	1.9%	1 mg 1 times / 10 min multiple, intravenous Recommended Dose: 1 mg, 1 times / 10 min Route: intravenous Route: multiple Dose: 1 mg, 1 times / 10 min Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	unhealthy, adult n = 776 Health Status: unhealthy Condition: atrial flutter or atrial fibrillation Age Group: adult Population Size: 776 Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf
Chest pain	2.6%	1 mg 1 times / 10 min multiple, intravenous Recommended Dose: 1 mg, 1 times / 10 min Route: intravenous Route: multiple Dose: 1 mg, 1 times / 10 min Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	unhealthy, adult n = 776 Health Status: unhealthy Condition: atrial flutter or atrial fibrillation Age Group: adult Population Size: 776 Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf
Hypotension	2.6%	1 mg 1 times / 10 min multiple, intravenous Recommended Dose: 1 mg, 1 times / 10 min Route: intravenous Route: multiple Dose: 1 mg, 1 times / 10 min Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	unhealthy, adult n = 776 Health Status: unhealthy Condition: atrial flutter or atrial fibrillation Age Group: adult Population Size: 776 Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf
Non-sustained ventricular tachycardia	3.4% Disc. AE	1 mg 1 times / 10 min multiple, intravenous Recommended Dose: 1 mg, 1 times / 10 min Route: intravenous Route: multiple Dose: 1 mg, 1 times / 10 min Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	unhealthy, adult n = 776 Health Status: unhealthy Condition: atrial flutter or atrial fibrillation Age Group: adult Population Size: 776 Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf
Non-sustained ventricular tachycardia	3.5% Disc. AE	1 mg 1 times / 10 min multiple, intravenous Recommended Dose: 1 mg, 1 times / 10 min Route: intravenous Route: multiple Dose: 1 mg, 1 times / 10 min Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	unhealthy, adult n = 776 Health Status: unhealthy Condition: atrial flutter or atrial fibrillation Age Group: adult Population Size: 776 Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf
Extrasystoles ventricular	3.7% Disc. AE	1 mg 1 times / 10 min multiple, intravenous Recommended Dose: 1 mg, 1 times / 10 min Route: intravenous Route: multiple Dose: 1 mg, 1 times / 10 min Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	unhealthy, adult n = 776 Health Status: unhealthy Condition: atrial flutter or atrial fibrillation Age Group: adult Population Size: 776 Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf
Headache	4.1%	1 mg 1 times / 10 min multiple, intravenous Recommended Dose: 1 mg, 1 times / 10 min Route: intravenous Route: multiple Dose: 1 mg, 1 times / 10 min Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	unhealthy, adult n = 776 Health Status: unhealthy Condition: atrial flutter or atrial fibrillation Age Group: adult Population Size: 776 Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf
Nausea	4.8%	1 mg 1 times / 10 min multiple, intravenous Recommended Dose: 1 mg, 1 times / 10 min Route: intravenous Route: multiple Dose: 1 mg, 1 times / 10 min Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf	unhealthy, adult n = 776 Health Status: unhealthy Condition: atrial flutter or atrial fibrillation Age Group: adult Population Size: 776 Sources: https://www.pfizer.ca/sites/default/files/201904/Corvert_PM_222103_29Mar2019_E.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737		substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12688833/ Page: 2.0	no
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12688833/ Page: 2.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.karger.com/Article/Pdf/111932

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY512832	https://www.001chemical.com/chem/122647-31-8
3B Scientific (Wuhan) Corp	3B2-1373	http://www.3bsc.com/index/pro_info.php?id=55089
AHH Chemical co.,ltd	MT-52774	http://www.ahhchemical.com/product/MT-52774.html
AK Scientific, Inc. (AKSCI)	71782	http://www.aksci.com/item_detail.php?cat=71782
AvaChem Scientific	2455B	http://www.avachem.com/productSearch.asp?2455B
BLD Pharm	BD134288	http://www.bldpharm.com/products/122647-31-8.html
BOC Sciences	122647-31-8	https://www.bocsci.com/ibutilide-cas-122647-31-8-item-56187.html
ChemMol	49421154	http://www.chemmol.com/chemmol/49421154.html
Finetech	FT-0631106	http://www.finetechnology-ind.com/prod/detail/pub/122647-31-8.html
Hairui	HR123088	http://www.hairuichem.com/en/product/122647-31-8.html
Molcore	MC512832	https://www.molcore.com/product/122647-31-8
OChem	23480	http://www.ocheminc.com/index.php?act=psearch&pid=647I318
Sinfoo Biotech	S007749	http://www.sinfoobiotech.com/product/1011147
Smolecule	S530325	http://www.smolecule.com/products/s530325
Smolecule	S580811	https://www.smolecule.com/products/s580811
THE BioTek	bt-269897	https://www.thebiotek.com/product/inhibitors/bt-269897
THE BioTek	bt-302102	https://www.thebiotek.com/product/others/bt-302102
eNovation Chemicals	D674346	https://www.enovationchem.com/ProductDetails.asp?ProductID=D674346
mcule	MCULE-5393489002	https://mcule.com/MCULE-5393489002/

PubMed

Title	Date	PubMed
Acute renal failure after ibutilide.	1999 Feb 6	9989724
Usefulness of ibutilide in facilitating successful external cardioversion of refractory atrial fibrillation.	1999 Nov 1	10569674
Termination of recent-onset atrial fibrillation/flutter in the emergency department: a sequential approach with intravenous ibutilide and external electrical cardioversion.	2000 Aug 1	10959017
Drug-induced QT prolongation in women during the menstrual cycle.	2001 Mar 14	11255387
[Severe ibutilide-induced arrhythmia in patients with heart failure].	2001 Oct 10	11706492
Comparison of verapamil and ibutilide for the suppression of immediate recurrences of atrial fibrillation after transthoracic cardioversion.	2002 Jul	12232564
Conversion of recent-onset atrial fibrillation or flutter with ibutilide after amiodarone has failed.	2002 Jul	12122531
Ibutilide-induced long QT syndrome and torsade de pointes.	2002 Nov-Dec	12424513
Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods.	2003 Aug 18	12873512
Structural determinants of HERG channel block by clofilium and ibutilide.	2004 Aug	15266014
Use of ibutilide in cardioversion of patients with atrial fibrillation or atrial flutter treated with class IC agents.	2004 Aug 18	15312873
The role of amiodarone in recent-onset atrial fibrillation after ibutilide has failed to restore sinus rhythm.	2007	17284902
Autonomic tone attenuates drug-induced QT prolongation.	2007 Sep	17666066
Relationship among amiodarone, new class III antiarrhythmics, miscellaneous agents and acquired long QT syndrome.	2008	18651412
Pharmacokinetics of ibutilide in patients with heart failure due to left ventricular systolic dysfunction.	2008 Dec	19025427
Pharmacology of the short QT syndrome N588K-hERG K+ channel mutation: differential impact on selected class I and class III antiarrhythmic drugs.	2008 Nov	18724381
Effects of ibutilide on inhibiting heart rate and rapidly terminating atrial flutter in canine.	2011 Apr	20972643

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Atrial Fibrillation 60 kg or more: 1 mg IV over 10 minutes; if arrhythmia persists 10 minutes after the end of the first infusion, repeat once. Less than 60 kg: 0.01 mg/kg IV over 10 minutes; if arrhythmia persists 10 minutes after the end of the first infusion, repeat once.

Route of Administration: Intravenous

In Vitro Use Guide

Ibutilide at the 10(-5) M effective refractory periods at 1 and 3 Hz increased by 18-32 ms, conduction times measured at 3 Hz increased by 27-30% and atrial rate decreased by 19-32% in isolated rabbit myocardium.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:21:12 UTC 2023` Edited by `admin` on `Fri Dec 15 16:21:12 UTC 2023`
Record UNII	9L5X4M5L6I
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

IBUTILIDE FUMARATE

Official Name

English

METHANESULFONAMIDE, N-(4-(4-(ETHYLHEPTYLAMINO)-1-HYDROXYBUTYL)PHENYL)-, (±)-, (E)-2-BUTENEDIOATE (2:1) (SALT)

Common Name

English

CORVERT

Brand Name

English

IBUTILIDE FUMARATE [MI]

Common Name

English

(±)-4'-(4-(ETHYLHEPTYLAMINO)-1-HYDROXYBUTYL)METHANESULFONANILIDE FUMARATE (2:1) (SALT)

Common Name

English

IBUTILIDE FUMARATE [ORANGE BOOK]

Common Name

English

IBUTILIDE FUMARATE [USP MONOGRAPH]

Common Name

English

IBUTILIDE FUMARATE [USAN]

Common Name

English

Ibutilide fumarate [WHO-DD]

Common Name

English

N-(4-(4-(ETHYLHEPTYLAMINO)-1-HYDROXYBUTYL)PHENYL)METHANESULFONAMIDE (E)-2-BUTENEDIOATE (2:1 SALT)

Common Name

English

IBUTILIDE FUMARATE [USP-RS]

Common Name

English

IBUTILIDE FUMARATE [VANDF]

Common Name

English

U-70226E

Code

English

IBUTILIDE FUMARATE [MART.]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C47793